Relationship between response and survival in more than 50,000 patients with advanced non-small cell lung cancer treated with systemic chemotherapy in 143 phase III trials.

Background: The association between the objective response to chemotherapy and survival has not yet been fully evaluated using large cohorts in advanced non-small cell lung cancer.

Methods: We searched for phase III trials conducted between 1991 and 2006 to investigate the role of systemic chemotherapy for advanced non-small cell lung cancer. Associations were tested by multiple regression analysis.

Results: Of the 1255 trials screened, 143 met our criteria, involving 50,569 patients with 309 chemotherapy regimens. In the first-line setting, the median intention-to-treat objective response rate (ORR) and disease control rate (DCR) were 26.4% and 62.5%, respectively (43,551 randomized patients; 290 trials). The median of the median survival time (MST) was 8.5 months in the first-line setting, and both the ORR and DCR were significantly associated with the MST in the multivariate analysis (regression coefficient = 0.0788 [p < 0.0001] and 0.0794 [p < 0.0001], respectively). Subgroup analysis showed no correlation between the ORR and MST in patients receiving chemotherapy containing molecular-targeted agents (p = 0.3817). In the second-line or later setting, the median ORR was only 6.8%, whereas the median DCR was 42.4% (4318 randomized patients; 19 trials). The median MST (6.6 months) was not associated with the ORR (p = 0.6992), but was associated with the DCR (p = 0.0129), despite the small sample size.

Conclusions: We found that survival was associated with both the ORR and DCR in the first-line setting, although it should be interpreted cautiously because of the abstracted data-based analysis. Regarding chemotherapy regimens containing molecular-targeted agents and salvage chemotherapy regimens, further assessments are warranted to clarify the association between the parameters.